The intention‐to‐treat effect of bridging treatments in the setting of Milan Criteria‐IN patients waiting for liver transplantation

In patients with hepatocellular cancer (HCC) meeting the Milan Criteria (MC), the benefit of loco-regional treatments (LRT) in the context of liver transplantation (LT) is still debated. Initial biases in the selection between treated and untreated patients have yielded conflicting reported results. The study aimed to identify, using a competing-risk analysis, risk factors for HCC-dependent LT failure, defined as pre-transplant tumor-related de-listing or post-transplant recurrence. The study was registered at http://www.ClinicalTrials.gov (ID:NCT03723304). In order to offset the initial limitations of the investigated population, an inverse probability of treatment weighting (IPTW) analysis was used: 1,083 MC-IN cases (no-LRT=182; LRT=901) were balanced using eight variables: age, gender, MELD value, HCV status, HBV status, largest lesion diameter, number of nodules, and alpha-fetoprotein (AFP). All the covariates were available at the first referral. After the IPTW, a pseudo-population of 2,019 patients listed for LT was analyzed, comparing two homogeneous groups of untreated (N=1,077) and LRT-treated (N=942) patients. Tumor progression after LRT was the most important independent risk factor for HCC-dependent failure (sub-hazard ratio=5.62; p<0.001). Other independent risk factors were major tumor diameter, AFP, MELD, patient age, male gender and period of waiting-list registration. One single LRT was protective compared with no treatment (SHR=0.51; p